cellular adaptation lecture has taken from Basis

1. Cellular Adaptation
Dr ALIYA ZAMAN

2. Adaptations are reversible changes in the size, number,
phenotype, metabolic activity, or functions of cells in
response to changes in their environment.

3. Hypertrophy
• Hypertrophy refers to an increase in the size of cells, that results in an
increase in the size of the affected organ.The hypertrophied organ has no
new cells, just larger cells.

4. • Hypertrophy can be physiologic or pathologic
• The former is caused by increased functional demand or by stimulation by
hormones and growth factors
• The most common stimulus for hypertrophy of muscle is increased
workload. For example, the bulging muscles of bodybuilders
• The massive physiologic growth of the uterus during pregnancy is a good
example of hormone-induced enlargement an organ

5. Mechanisms of Hypertrophy
• Hypertrophy is the result of increased production of cellular proteins. Much
of our understanding of hypertrophy is based on studies of the heart

8. There are three basic steps in the molecular
pathogenesis of cardiac hypertrophy
1. The integrated actions of mechanical sensors (that are triggered by
increased workload), growth factors (includingTGF-β, insulin-like growth
factor 1 [IGF1], fibroblast growth factor), and vasoactive agents (e.g., α-
adrenergic agonists, endothelin-1, and angiotensin II).
2. These signals originating in the cell membrane activate a complex web of
signal transduction pathways i.e phosphoinositide 3-kinase (PI3K)/ AKT
pathway
3. These signaling pathways activate a set of transcription factors such as
GATA4, nuclear factor of activatedT cells (NFAT), and myocyte enhancer
factor 2 (MEF2).

9. • These transcription factors work coordinately to increase the synthesis of
muscle proteins that are responsible for hypertrophy.
• Hypertrophy is also associated with a switch of contractile proteins from
adult to fetal or neonatal forms.
• For example, during muscle hypertrophy, the α isoform of myosin heavy
chain is replaced by the β isoform
• Cardiac hypertrophy is associated with increased atrial natriuretic factor
gene expression

10. • Whatever the exact cause and mechanism of cardiac hypertrophy, it
eventually reaches a limit beyond which enlargement of muscle mass is no
longer able to cope with the increased burden.
• At this stage several regressive changes occur in the myocardial fibers, of
which the most important are lysis and loss of myofibrillar contractile
elements.
• In extreme cases myocyte death can occur.
• The net result of these changes is cardiac failure, a sequence of events that
illustrates how an adaptation to stress can progress to functionally
significant cell injury

12. Hyperplasia
• Most forms of pathologic hyperplasia are caused by excessive or
inappropriate actions of hormones or growth factors acting on target cells
• Endometrial hyperplasia is an example of abnormal hormone-induced
hyperplasia.

13. Physiological hyperplasia
• Increase in the size of the breasts during pregnancy, increase in thickness of
endometrium during menstrual cycle, and liver growth after partial
resection.

16. Pathological
• Most forms of pathologic hyperplasia are caused by excessive or
inappropriate actions of hormones or growth factors acting on target cells
• Endometrial hyperplasia is an example of abnormal hormone-induced
hyperplasia
• IF the balance between estrogen and progesterone is disturbed, resulting in
absolute or relative increases in the amount of estrogen, with consequent
hyperplasia of the endometrial glands.
• This form of pathologic hyperplasia is a common cause of abnormal
menstrual bleeding.

17. Endometrial hyperplasia is an example of abnormal
hormone-induced hyperplasia.

20. • Benign prostatic hyperplasia is another common example of pathologic
hyperplasia induced in responses to hormonal stimulation by androgens.

23. • Hyperplasia is a characteristic response to certain viral infections, such as
papillomaviruses, which cause skin warts and several mucosal lesions
composed of masses of hyperplastic epithelium.

27. Mechanisms of Hyperplasia
• Hyperplasia is the result of growth factor-driven proliferation of mature
cells and, in some cases, by increased output of new cells from tissue stem
cells
• For instance, after partial hepatectomy growth factors are produced in the
liver that engage receptors on the surviving cells and activate signaling
pathways that stimulate cell proliferation.

29. Atrophy
Atrophy is defined as a reduction in the size of an organ or
tissue due to a decrease in cell size and number. Atrophy
can be physiologic or pathologic

30. Physiologic atrophy
• It is common during normal development.
• Some embryonic structures, such as the notochord and thyroglossal duct,
undergo atrophy during fetal development.
• The decrease in the size of the uterus that occurs shortly after parturition is
another form of physiologic atrophy

31. • Pathologic atrophy has several causes and it can be local or generalized.
1. Decreased workload (atrophy of disuse).
2. Loss of innervation (denervation atrophy)
3. Inadequate nutrition
4. Loss of endocrine stimulation
5. Pressure.

35. • Early in the process atrophic cells and tissues have diminished function, but
cell death is minimal.

36. Mechanisms of Atrophy
• Atrophy results from decreased protein synthesis and increased protein
degradation in cells.
• The degradation of cellular proteins occurs mainly by the ubiquitin-
proteasome pathway
• In many situations, atrophy is also accompanied by increased autophagy,
marked by the appearance of increased numbers of autophagic vacuoles
• It may persist in the cytoplasm as membrane-bound residual bodies. An
example of residual bodies is lipofuscin granules

39. Metaplasia
• Metaplasia is a reversible change in which one differentiated cell type (epithelial or
mesenchymal) is replaced by another cell type
• The most common epithelial metaplasia is columnar to squamous as occurs in the
respiratory tract in response to chronic irritation
• In the habitual cigarette smoker, the normal ciliated columnar epithelial cells of the
trachea and bronchi are often replaced by stratified squamous epithelial cells.
• Stones in the excretory ducts of the salivary glands, pancreas, or bile ducts, which
are normally lined by secretory columnar epithelium, may also lead to squamous
metaplasia by stratified squamous epithelium
• A deficiency of vitamin A (retinoic acid) induces squamous metaplasia in the
respiratory epithelium

45. • Connective tissue metaplasia is the formation of cartilage, bone, or adipose
tissue (mesenchymal tissues) in tissues that normally do not contain these
elements. For example, bone formation in muscle, designated myositis
ossificans,

48. Mechanisms of Metaplasia
• It is the result of a reprogramming of stem cells that are known to exist in
normal tissues, or of undifferentiated mesenchymal cells present in
connective tissue.
• In a metaplastic change, these precursor cells differentiate along a new
pathway.